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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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1 term
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Biochemical function
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hormone activity
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1 term
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DOI no:
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Biophys J
63:1210-1220
(1992)
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PubMed id:
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Conformational changes in cubic insulin crystals in the pH range 7-11.
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O.Gursky,
J.Badger,
Y.Li,
D.L.Caspar.
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ABSTRACT
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To determine the effect of variations in the charge distribution on the
conformation of a protein molecule, we have solved the structures of bovine
cubic insulin over a pH range from 7 to 11 in 0.1 M and 1 M sodium salt
solutions. The x-ray data were collected beyond 2-A resolution and the R factors
for the refined models ranged from 0.16 to 0.20. Whereas the positions of most
protein and well-ordered solvent atoms are conserved, about 30% of residues
alter their predominant conformation as the pH is changed. Conformational
switching of A5 Gln and B10 His correlates with the pH dependence of monovalent
cation binding to insulin in cubic crystals. Shifts in the relative positions of
the A chain NH2-terminal and B chain COOH-terminal groups are probably due to
titration of the A1 alpha-amino group. Two alternative positions of B25 Phe and
A21 Asn observed in cubic insulin at pH 11 are similar to those found in two
independent molecules of the 2Zn insulin dimer at pH 6.4. The conformational
changes of the insulin amino acids appear to be only loosely coupled at distant
protein sites. Shifts in the equilibrium between distinct conformational
substates as the charge distribution on the protein is altered are analogous to
the electrostatically triggered movements that occur in many functional protein
reactions.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.Fufezan,
and
M.Specht
(2009).
p3d--Python module for structural bioinformatics.
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BMC Bioinformatics, 10,
258.
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K.Maeda,
P.Hägglund,
C.Finnie,
B.Svensson,
and
A.Henriksen
(2006).
Structural basis for target protein recognition by the protein disulfide reductase thioredoxin.
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Structure, 14,
1701-1710.
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PDB code:
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M.D.Leavell,
P.Novak,
C.R.Behrens,
J.S.Schoeniger,
and
G.H.Kruppa
(2004).
Strategy for selective chemical cross-linking of tyrosine and lysine residues.
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J Am Soc Mass Spectrom, 15,
1604-1611.
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B.V.Prasad,
and
K.Suguna
(2003).
Effect of pH on the structure of rhizopuspepsin.
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Acta Crystallogr D Biol Crystallogr, 59,
1755-1761.
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PDB codes:
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J.Diao
(2003).
Crystallographic titration of cubic insulin crystals: pH affects GluB13 switching and sulfate binding.
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Acta Crystallogr D Biol Crystallogr, 59,
670-676.
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PDB codes:
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R.Berisio,
F.Sica,
V.S.Lamzin,
K.S.Wilson,
A.Zagari,
and
L.Mazzarella
(2002).
Atomic resolution structures of ribonuclease A at six pH values.
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Acta Crystallogr D Biol Crystallogr, 58,
441-450.
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PDB codes:
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J.J.Havranek,
and
P.B.Harbury
(1999).
Tanford-Kirkwood electrostatics for protein modeling.
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Proc Natl Acad Sci U S A, 96,
11145-11150.
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B.Yu,
and
D.L.Caspar
(1998).
Structure of cubic insulin crystals in glucose solutions.
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Biophys J, 74,
616-622.
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C.M.Yip,
and
M.D.Ward
(1996).
Atomic force microscopy of insulin single crystals: direct visualization of molecules and crystal growth.
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Biophys J, 71,
1071-1078.
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J.Badger,
A.Kapulsky,
O.Gursky,
B.Bhyravbhatla,
and
D.L.Caspar
(1994).
Structure and selectivity of a monovalent cation binding site in cubic insulin crystals.
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Biophys J, 66,
286-292.
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J.Badger,
Y.Li,
and
D.L.Caspar
(1994).
Thallium counterion distribution in cubic insulin crystals determined from anomalous x-ray diffraction data.
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Proc Natl Acad Sci U S A, 91,
1224-1228.
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O.Gursky,
E.Fontano,
B.Bhyravbhatla,
and
D.L.Caspar
(1994).
Stereospecific dihaloalkane binding in a pH-sensitive cavity in cubic insulin crystals.
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Proc Natl Acad Sci U S A, 91,
12388-12392.
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J.Badger
(1993).
Multiple hydration layers in cubic insulin crystals.
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Biophys J, 65,
1656-1659.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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